Berlin Institute of Health Center for Regenerative Therapies (BCRT): Berlin-Brandenburger Centrum für Regenerative Therapien, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Systems Immunology Lab, Department of Biology, Humboldt-Universität zu Berlin, Berlin, Germany.
Sci Rep. 2020 Nov 11;10(1):19594. doi: 10.1038/s41598-020-76607-z.
Epstein-Barr virus (EBV) reactivation can lead to serious complications in kidney transplant patients, including post-transplant lymphoproliferative disorder (PTLD). Here, we have assessed the impact of EBV on B cell homeostasis at cellular and humoral level. In a multicenter study monitoring 540 kidney transplant patients during the first post-transplant year, EBV reactivation was detected in 109 patients. Thirteen soluble factors and B cell counts were analyzed in an EBV sub-cohort (N = 54) before, at peak and after EBV clearance and compared to a control group (N = 50). The B cell activating factor (BAFF) was significantly elevated among EBV patients. No additional soluble factors were associated with EBV. Importantly, in vitro experiments confirmed the proliferative effect of BAFF on EBV-infected B cells, simultaneously promoting EBV production. In contrast, elevated levels of BAFF in EBV patients did not lead to B cell expansion in vivo. Moreover, diminished positive inter-correlations of soluble factors and alterations of the bi-directional interplay between B cell and soluble factors were observed in EBV patients at peak and after clearance. Our data suggest that such alterations may counteract the proliferative effect of BAFF, preventing B cell expansion. The role of these alterations in lymphoma development should be analyzed in future studies.
EB 病毒（EBV）的再激活可导致肾移植患者出现严重并发症，包括移植后淋巴组织增生性疾病（PTLD）。在此，我们评估了 EBV 对 B 细胞在细胞和体液水平上的稳态的影响。在一项监测 540 例肾移植患者在移植后第一年的多中心研究中，有 109 例患者出现 EBV 再激活。在 EBV 亚组（N=54）中，我们在 EBV 清除之前、达到峰值时和之后分析了 13 种可溶性因子和 B 细胞计数，并与对照组（N=50）进行了比较。EBV 患者的 B 细胞激活因子（BAFF）显著升高。没有其他可溶性因子与 EBV 相关。重要的是，体外实验证实 BAFF 对 EBV 感染的 B 细胞具有增殖作用，同时促进 EBV 的产生。相比之下，EBV 患者中 BAFF 水平的升高并没有导致体内 B 细胞的扩增。此外，在 EBV 患者达到峰值和清除后，观察到可溶性因子之间的正相关性降低，以及 B 细胞与可溶性因子之间的双向相互作用发生改变。我们的数据表明，这些改变可能会抵消 BAFF 的增殖作用，从而防止 B 细胞的扩增。未来的研究应该分析这些改变在淋巴瘤发展中的作用。
